How extracellular (hormonal, sensory or neuronal) signals regulate differentiation is a central question of cellular and developmental biology. We are interested in understanding how events at the cell surface ultimately manifest alterations in gene activity and cell fate. Dictyostelium has proven an excellent system for studying such mechanisms, lending itself to molecular, cellular, biochemical and genetic manipulation. Several aspects are being explored. We have continued our molecular analysis of genes which encode proteins required for signal transduction. Primarily, this has involved studies on the function and expression of a number of G-protein linked, cell surface receptors. We have isolated four receptor genes; each exhibits a distinct pattern of temporal and spatial expression during the Dictyostelium developmental cycle. Structural and functional analyses suggest that they couple to different effector systems. We have also tentatively identified several other genes which may encode additional receptors that interact with G-proteins. In a complementary approach, we have begun an analysis of hormonal regulation of mammalian differentiation, focusing on the isolation, regulation and function of genes expressed specifically in adipocytes. We have isolated several cDNAs which appear to be derived from mRNAs which encode a fat-associated protein preferentially expressed in adipocytes. Other adipocyte proteins of interest include hormone sensitive glucose transporter, lipoprotein lipase and hormone sensitive lipase. Preliminary results indicate that the genes for these proteins are differentially regulated in cultured adipocytes.